"CHEK2 and p53 Mutations in African Americans" One of the largest collections of Afr. American families at high risk of hereditary breast cancer is available at Howard to investigate breast cancer predisposing mutations. CHEK2 and p53 participate in the DNA repair pathway initiated by Ataxia telangiectasia and may account for some of the unexplained risk of hereditary breast cancer. The entire coding and intron flanking regions of CHEK2 and p53 will be screened for germline mutations in non-BRCA1/2 high-risk Afr. American patients using denaturing high performance liquid chromatography. Mutations observed in patients will be tested in family members and cancer-free Afr. American controls and mutation frequencies compared. Mutations in conserved splice sites and exon specific enhancers will be tested for effects on splicing. Mutations in p53 will be tested for effects on growth, cell cycle arrest, and transcription. Because of known genetic variation, a large number of distinct germline mutations are expected in Afr. Americans, some of which are predicted to be ethnic-specific. This study will provide information about the spectrum of mutations for genetic testing, genetic counseling, and risk assessment.